DESCRIPTION, OVERALL (provided by applicant): The UNC MTCC Program has selected a configuration of six Cores and three Pilot &Feasibility Project to synergize and accelerate the progress of molecular therapy research at UNC CH. The Administrative Core (Core A, R.C. Boucher, P.I.) will oversee and coordinate all aspects of the MTCC operation, including the operation of Core facilities and the selection and oversight of the Pilot &Feasibility Program. In addition, this Core will interface with other important activities on the UNC CH campus, including training and clinical trials networks. Each Core will provide novel and important services to the UNC CH molecular therapeutics community. The Vector Core (Core B, J. Beecham, P.I.) will provide new vectors (double-stranded, shuffled, chimeric AAV, high capacity adenoviral, paramyxovirus) and services (plasmid preparation). The Molecular Biology and Mouse Core (Core C, W. O'Neal, P.I.) will provide mice with CF like lung disease ((3ENaC and pENaC/CF mice) and shRNA technologies. The Imaging Core (Core D, C.W. Davis, P.I.) will provide a range of new imaging technologies, as well as histology and EM capabilities. The Correction Core (Core E, S.E. Gabriel, P.I.) will provide UNC CH investigators with a wide range of airway and G.I. assays to detect correction of CF defects both in in vivo and in vitro systems. The Cell Models Core (Core F, S. Randell, P.I.) will provide additional cell types to the MTCC community, e.g., airway and G.I. stem cells, as well as novel airway immortalized cell lines. The Cores will be supplemented by three Pilot &Feasibility Projects. P&F 7 (L. Ostrowski, P.I.), in collaboration with Drs. Olsen and Kafri, will explore the efficiency requirements for correcting with lentiviruses diseases characterized as "ciliopathies". P&F 8 (A. Asokan, P.I.), in collaboration with Dr. Samulski, will explore the targeting of G.I. epithelia, including stem cells, for CF mouse gut correction. P&F 9 (J. Olsen, P.I.) will, in collaboration with Dr. Grubb, test the efficiency of integrating vs. non-integrating EIAV lentiviral vectors in correcting the neonatal phenotype of the CF-like (3ENaC/AF508 CF mouse lung. The MTCC is complemented at UNC by an environment rich in basic science, translational research, and training that will guarantee maximal utilization of MTCC resources. PUBLIC HEALTH RELEVANCE: Cystic fibrosis is the most common lethal genetic disease affecting Caucasian Americans. The efforts of the MTCC are dedicated towards developing gene therapy technologies designed to arrest or even cure this disease.